RESUMO
Sustainable TGF-ß1 signaling drives organ fibrogenesis. However, the cellular adaptation to maintain TGF-ß1 signaling remains unclear. In this study, we revealed that dietary folate restriction promoted the resolution of liver fibrosis in mice with nonalcoholic steatohepatitis. In activated hepatic stellate cells, folate shifted toward mitochondrial metabolism to sustain TGF-ß1 signaling. Mechanistically, nontargeted metabolomics screening identified that α-linolenic acid (ALA) is exhausted by mitochondrial folate metabolism in activated hepatic stellate cells. Knocking down serine hydroxymethyltransferase 2 increases the bioconversion of ALA to docosahexaenoic acid, which inhibits TGF-ß1 signaling. Finally, blocking mitochondrial folate metabolism promoted liver fibrosis resolution in nonalcoholic steatohepatitis mice. In conclusion, mitochondrial folate metabolism/ALA exhaustion/TGF-ßR1 reproduction is a feedforward signaling to sustain profibrotic TGF-ß1 signaling, and targeting mitochondrial folate metabolism is a promising strategy to enforce liver fibrosis resolution.
Assuntos
Ácido Fólico , Cirrose Hepática , Mitocôndrias , Ácido alfa-Linolênico , Animais , Camundongos , Ácido alfa-Linolênico/deficiência , Ácido alfa-Linolênico/metabolismo , Células Estreladas do Fígado/metabolismo , Fígado/citologia , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/complicações , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Ácido Fólico/metabolismo , Mitocôndrias/metabolismo , Deficiência de Ácido Fólico/complicações , Deficiência de Ácido Fólico/metabolismo , Transdução de Sinais , Retroalimentação FisiológicaRESUMO
Previous studies on rats and human subjects have established that the linoleic acid (LA) requirement is 2 % of the total energy intake (en%), but is obtained in the absence of α-linolenic acid (ALA) and consequently appear to be overestimated. This raises questions since a recent study including ALA has suggested to divide the historical value by four. However, this recent study has remained inconclusive because the animals used were not totally LA-deficient animals. For the first time, the present study was especially designed using physiological and biochemical markers and performed in two steps: (1) to achieve a specific n-6 fatty acid deficiency model using growing male rats fed either a 0 en% from LA/0 en% from ALA (0LA/0ALA), 0LA/0·5ALA or 2LA/0·5ALA diet, born from female rats fed a 0LA/0·5ALA diet; and (2) to refine the required level of LA in the presence of ALA using rats fed either a 0LA/0ALA, 0·5LA/0·5ALA, 1LA/0·5ALA, 1·5LA/0·5ALA diet, born from female rats fed a 0LA/0·5ALA diet. The first step shows that the best LA deficiency model was obtained using rats fed the 0LA/0ALA diet, born from female rats fed the 0LA/0·5ALA diet. The second step demonstrates that in growing rats, LA deficiency was corrected with an intake of 1-1·5 en% from LA and 0·5 en% from ALA. These data suggest that the requirements in humans should be revisited, considering the presence of ALA to set up the recommendation for LA.
Assuntos
Deficiências Nutricionais/prevenção & controle , Modelos Animais de Doenças , Ingestão de Energia , Ácido Linoleico/uso terapêutico , Necessidades Nutricionais , Ácido alfa-Linolênico/administração & dosagem , Animais , Biomarcadores , Deficiências Nutricionais/dietoterapia , Deficiências Nutricionais/fisiopatologia , Feminino , Desenvolvimento Fetal , Lactação , Ácido Linoleico/administração & dosagem , Ácido Linoleico/deficiência , Ácido Linoleico/metabolismo , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Distribuição Aleatória , Ratos Wistar , Dermatopatias Metabólicas/etiologia , Dermatopatias Metabólicas/prevenção & controle , Cauda , Desmame , Aumento de Peso , Ácido alfa-Linolênico/deficiência , Ácido alfa-Linolênico/metabolismoRESUMO
Diminished levels of docosahexaenoic acid (22:6n-3), the major fatty acid (FA) synthesized from alpha-linolenic acid (18:3n-3), have been implicated in functional impairment in the developing and adult brain. We have now examined the changes in phospholipid (PL) molecular species in the developing postnatal cortex, a region recently shown to be affected by a robust aberration in neuronal cell migration, after maternal diet alpha-linolenic acid deprivation (Yavin et al. (2009)Neuroscience162(4),1011). The frontal cortex PL composition of 1- to 4-week-old rats was analyzed by gas chromatography and electrospray ionization/tandem mass spectrometry. Changes in the cortical PL molecular species profile by dietary means appear very specific as 22:6n-3 was exclusively substituted by docosapentaenoic acid (22:5n-6). However, molecular species were conserved with respect to the combination of specific polar head groups (i.e. ethanolamine and serine) in sn-3 and defined saturated/mono-unsaturated FA in sn-1 position even when the sn-2 FA moiety underwent diet-induced changes. Our results suggest that substitution of docosahexaenoic acid by docosapentaenoic acid is tightly regulated presumably to maintain a proper biophysical characteristic of membrane PL molecular species. The importance of this conservation may underscore the possible biochemical consequences of this substitution in regulating certain functions in the developing brain.
Assuntos
Córtex Cerebral/crescimento & desenvolvimento , Córtex Cerebral/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Neurogênese/fisiologia , Fosfolipídeos/metabolismo , Ácido alfa-Linolênico/deficiência , Animais , Animais Recém-Nascidos , Córtex Cerebral/química , Córtex Cerebral/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/química , Feminino , Humanos , Neurogênese/efeitos dos fármacos , Fosfolipídeos/química , Gravidez , Ratos , Ratos Wistar , Ácido alfa-Linolênico/administração & dosagem , Ácido alfa-Linolênico/químicaRESUMO
Decreased tissue levels of docosahexaenoic acid (DHA; 22:6n-3) are implicated in the etiologies of non-puerperal and postpartum depression. With the aim of determining neurobiological sequelae of decreased brain DHA content, this study examined the effects of a loss of brain DHA content and concurrent reproductive status in adult female Long-Evans rats. An alpha-linolenic acid-deficient diet and breeding protocols were used to produce virgin and parous female rats with cortical phospholipid DHA levels 23-26% lower than virgin and parous rats fed a control diet containing adequate alpha-linolenic acid. Parous dams were tested/euthanized at weaning (postnatal day 20) of the second litter; virgin females, during diestrus. Decreased brain DHA was associated with decreased hippocampal BDNF gene expression and increased relative corticosterone response to an intense stressor, regardless of reproductive status. In virgin females with decreased brain DHA, serotonin content and turnover in frontal cortex were decreased compared to virgin females with normal brain DHA. In parous dams with decreased brain DHA, the density of 5-HT(1A) receptors in the hippocampus was increased, corticosterone response to an intense stressor was increased, and the latency to immobility in the forced swim test was decreased compared to parous dams with normal DHA. These findings demonstrate neurobiological alterations attributable to decreased brain DHA or an interaction of parous status and brain DHA level. Furthermore, the data are consistent with findings in depressed humans, and thus support a role for DHA as a factor in the etiologies of depressive illnesses, particularly postpartum depression.
Assuntos
Encéfalo/metabolismo , Corticosterona/metabolismo , Depressão/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Estresse Psicológico/metabolismo , Adaptação Fisiológica , Análise de Variância , Animais , Química Encefálica , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão Pós-Parto/metabolismo , Feminino , Lobo Frontal/metabolismo , Regulação da Expressão Gênica/fisiologia , Hipocampo/metabolismo , Masculino , Fosfolipídeos/análise , Fosfolipídeos/metabolismo , RNA/análise , Ratos , Ratos Long-Evans , Receptor 5-HT1A de Serotonina/metabolismo , Reprodução/fisiologia , Serotonina/metabolismo , Ácido alfa-Linolênico/deficiênciaRESUMO
BACKGROUND: High-oleic (HO) seed oils are being introduced as replacements for trans fatty acid (TFA)-containing fats and oils. Negative health effects associated with TFAs led to their removal from the US Generally Recognized As Safe list. HO oils formulated for use in food production may result in changes in fatty acid intake at population levels. Objectives: The purposes of this study were to 1) identify major food sources of soybean oil (SO) and canola oil (CO), 2) estimate effects of replacing SO and CO with HO varieties on fatty acid intake overall and by age and sex strata, and 3) compare predicted intakes with the Dietary Reference Intakes and Adequate Intakes (AIs) for the essential fatty acids (EFAs) α-linolenic acid (ALA) and linoleic acid (LA). Design: Food and nutrient intakes from NHANES waves 2007-2008, 2009-2010, 2011-2012, and 2013-2014 in 21,029 individuals aged ≥20 y were used to model dietary changes. We estimated the intake of fatty acid with the replacement of HO-SO and HO-CO for commodity SO and CO at 10%, 25%, and 50% and evaluated the potential for meeting the AI at these levels. RESULTS: Each modeling scenario decreased saturated fatty acids (SFAs), although intakes remained greater than recommended for all age and sex groups. Models of all levels increased the intake of total monounsaturated fatty acids (MUFAs), especially oleic acid, and decreased the intake of total polyunsaturated fatty acids (PUFAs), particularly LA and ALA. Replacement of traditional with HO oils at 25-50% places specific adult age and sex groups at risk of not meeting the AI for LA and ALA. Conclusions: The replacement of traditional oils with HO varieties will increase MUFA intake and reduce both SFA and PUFA intakes, including EFAs, and may place specific age and sex groups at risk of inadequate LA and ALA intake.
Assuntos
Gorduras Insaturadas na Dieta/administração & dosagem , Ácidos Graxos Insaturados/administração & dosagem , Ácidos Graxos/administração & dosagem , Ácido Oleico/administração & dosagem , Óleo de Brassica napus/análise , Óleo de Soja/análise , Adulto , Idoso , Dieta , Gorduras Insaturadas na Dieta/análise , Ácidos Graxos/análise , Ácidos Graxos Monoinsaturados/administração & dosagem , Ácidos Graxos Insaturados/análise , Feminino , Humanos , Lactação , Ácido Linoleico/administração & dosagem , Ácido Linoleico/deficiência , Masculino , Pessoa de Meia-Idade , Política Nutricional , Inquéritos Nutricionais , Ácido Oleico/análise , Gravidez , Fatores de Risco , Ácidos Graxos trans/administração & dosagem , Ácidos Graxos trans/análise , Ácido alfa-Linolênico/administração & dosagem , Ácido alfa-Linolênico/deficiênciaRESUMO
Failure to provide omega 3 fatty acids in the perinatal period results in alterations in nerve growth factor levels, dopamine production and permanent elevations in blood pressure. The present study investigated whether changes in brain (i.e., hypothalamus) glycerophospholipid fatty acid profiles induced by a diet rich in omega 6 fatty acids and very low in alpha-linolenic acid (ALA) during pregnancy and the perinatal period could be reversed by subsequent feeding of a diet containing ALA. Female rats (6 per group) were mated and fed either a low ALA diet or a control diet containing ALA throughout pregnancy and until weaning of the pups at 3 weeks. At weaning, the pups (20 per group) remained on the diet of their mothers until 9 weeks, when half the pups were switched onto the other diet, thus generating four groups of animals. At 33 weeks, pups were killed, the hypothalamus dissected from the male rats and analysed for glycerophospholipid fatty acids. In the animals fed the diet with very little ALA and then re-fed the control diet containing high levels of ALA for 24 weeks, the DHA levels were still significantly less than the control values in PE, PS and PI fractions, by 9%, 18% and 34%, respectively. In this group, but not in the other dietary groups, ALA was detected in all glycerophospholipid classes at 0.2-1.7% of the total fatty acids. The results suggest that omega 6-3 PUFA imbalance early in life leads to irreversible changes in hypothalamic composition. The increased ALA and reduced DHA proportions in the animals re-fed ALA in later life are consistent with a dysfunction or down-regulation of the conversion of ALA to 18:4n-3 by the delta-6 desaturase.
Assuntos
Dieta , Ácidos Graxos Ômega-6/administração & dosagem , Glicerofosfolipídeos/química , Hipotálamo/química , Ácido alfa-Linolênico/administração & dosagem , Ácido alfa-Linolênico/deficiência , Animais , Dieta/efeitos adversos , Gorduras Insaturadas na Dieta/administração & dosagem , Gorduras Insaturadas na Dieta/análise , Ácidos Docosa-Hexaenoicos/análise , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/análise , Ácidos Graxos Ômega-6/análise , Feminino , Glicerofosfolipídeos/análise , Hipotálamo/crescimento & desenvolvimento , Masculino , Troca Materno-Fetal , Gravidez , Fenômenos Fisiológicos da Nutrição Pré-Natal , Ratos , TempoRESUMO
BACKGROUND: Several animal experiments have documented that omega-3 fatty acid alpha-linolenic acid (ALA) (C 18:3, n-3) from vegetable oils has beneficial electrophysiological and antiarrhythmic effects. This may explain the protective effect of ALA against cardiovascular diseases and sudden death. MATERIALS AND METHODS: We have continuously and systematically collected and evaluated relevant literature (observational and secondary prophylactic studies) and here present an overview of the effects of ALA on cardiovascular diseases and sudden death. RESULTS: Several observational studies in healthy individuals and in patients with coronary heart disease have indicated that a diet rich in ALA reduces coronary death and the risk for sudden death. A cross-sectional study has shown a beneficial effect of ALA on the progression of coronary atherosclerosis. Three secondary studies have also indicated beneficial effects of ALA on several cardiovascular end-points. Diet studies do have limitations, and the secondary prophylactic studies have not given a definite answer to whether ALA possesses beneficial cardiovascular effects. INTERPRETATION: On the whole, the observational and secondary prophylactic studies indicate that ALA may have cardioprotective effects in healthy individuals and in patients with coronary heart disease. For those who seldom eat fish and only take small amounts of fish oils, a diet rich on ALA may be an alternative.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Morte Súbita Cardíaca/prevenção & controle , Ácido alfa-Linolênico/administração & dosagem , Adulto , Idoso , Doença da Artéria Coronariana/prevenção & controle , Dieta Mediterrânea , Medicina Baseada em Evidências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevenção Primária , Ensaios Clínicos Controlados Aleatórios como Assunto , Ácido alfa-Linolênico/deficiênciaRESUMO
The fatty acids, linoleic acid (18:2ω-6) and α-linolenic acid (18:3ω-3), are essential to the human diet. When these essential fatty acids are not provided in sufficient quantities, essential fatty acid deficiency (EFAD) develops. This can be suggested clinically by abnormal liver function tests or biochemically by an elevated Mead acid and reduced linoleic acid and arachidonic acid level, which is manifested as an elevated triene/tetraene ratio of Mead acid/arachidonic acid. Clinical features of EFAD may present later. With the introduction of novel intravenous (IV) lipid emulsions in North America, the proportion of fatty acids provided, particularly the essential fatty acids, varies substantially. We describe a case series of 3 complicated obese patients who were administered parenteral nutrition (PN), primarily using ClinOleic 20%, an olive oil-based lipid emulsion with reduced amounts of the essential fatty acids, linoleic and α-linolenic, compared with more conventional soybean oil emulsions throughout their hospital admission. Essential fatty acid profiles were obtained for each of these patients to investigate EFAD as a potential cause of abnormal liver enzymes. Although the profiles revealed reduced linoleic acid and elevated Mead acid levels, this was not indicative of the development of essential fatty acid deficiency, as reflected in the more definitive measure of triene/tetraene ratio. Instead, although the serum fatty acid panel reflected the markedly lower but still adequate dietary linoleic acid content and greatly increased oleic acid content in the parenteral lipid emulsion, the triene/tetraene ratio remained well below the level, indicating EFAD in each of these patients. The availability and use of new IV lipid emulsions in PN should encourage the clinician to review lipid metabolism based on the quantity of fatty acids provided in specific parenteral lipid emulsions and the expected impact of these lipid emulsions (with quite different fatty acid composition) on measured fatty acid profiles.
Assuntos
Deficiências Nutricionais/etiologia , Gorduras Insaturadas na Dieta , Emulsões Gordurosas Intravenosas/efeitos adversos , Ácidos Graxos Essenciais , Fígado/efeitos dos fármacos , Nutrição Parenteral/efeitos adversos , Óleos de Plantas/efeitos adversos , Óleo de Soja/efeitos adversos , Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Ácido 8,11,14-Eicosatrienoico/sangue , Ácido Araquidônico/sangue , Deficiências Nutricionais/sangue , Gorduras Insaturadas na Dieta/administração & dosagem , Gorduras Insaturadas na Dieta/efeitos adversos , Gorduras Insaturadas na Dieta/sangue , Emulsões Gordurosas Intravenosas/química , Ácidos Graxos Essenciais/administração & dosagem , Ácidos Graxos Essenciais/sangue , Ácidos Graxos Essenciais/deficiência , Humanos , Ácido Linoleico/administração & dosagem , Ácido Linoleico/sangue , Ácido Linoleico/deficiência , Fígado/enzimologia , Ácido Oleico/administração & dosagem , Ácido Oleico/sangue , Óleo de Soja/sangue , Ácido alfa-Linolênico/administração & dosagem , Ácido alfa-Linolênico/sangue , Ácido alfa-Linolênico/deficiênciaRESUMO
Growth cones are membrane-rich structures found at the distal end of growing axons and are the predecessors of the synaptic membranes of nerve endings. This study examined whether n-3 fatty acid restriction during gestation in rats alters the composition of growth cone and neuronal cell body membrane fatty acids in newborns. Female rats were fed a standard control diet containing soy oil (8% of fatty acids as 18:3n-3 by wt) or a semisynthetic n-3 fatty acid-deficient diet with safflower oil (0.3% of fatty acids as 18:3n-3 by wt) throughout normal pregnancy. Experiments were conducted on postnatal day 2 to minimize the potential for contamination from synaptic membranes and glial cells. Dietary n-3 fatty acid restriction resulted in lower docosahexaenoic acid (DHA) concentrations and a corresponding higher docosapentaenoic acid concentration in neuronal growth cones, but had no effects on neuronal cell body fatty acid concentrations. These studies suggest that accretion of DHA in growth cones, but not neuronal cell bodies, is affected by n-3 fatty acid restriction during gestation. Differences in other fatty acids or components between the semisynthetic and the standard diet, however, could have been involved in the effects on growth-cone DHA content. The results also provide evidence to suggest that the addition of new membrane fatty acids to neurons during development occurs along the shaft of the axon or at the growth cone, rather than originating at the cell body.
Assuntos
Dieta com Restrição de Gorduras/efeitos adversos , Ácidos Graxos Ômega-3/fisiologia , Cones de Crescimento/química , Neurônios/química , Ácido alfa-Linolênico/deficiência , Animais , Animais Recém-Nascidos , Química Encefálica , Cromatografia Gasosa , Ácidos Docosa-Hexaenoicos/análise , Feminino , Gravidez , Ratos , Ratos WistarRESUMO
PURPOSE: Docosahexaenoic acid (DHA) is the major polyunsaturated fatty acid within rod outer segments. Varying the dietary content of DHA or its precursor, alpha-linolenic acid (ALA), can alter retinal DHA levels. The purpose of the present study was to assess rod phototransduction and recovery in rhesus monkeys raised on diets with different DHA and ALA content. METHODS: Adult rhesus monkeys had consumed from birth a diet low in ALA (0.3%) and known to induce an 80% reduction in retinal DHA. They were compared with groups receiving 8% ALA or 0.6% DHA, both of which support normal retinal DHA levels. Rod recovery was assessed with a double-flash protocol using a-wave saturating test flashes. The recovery of rod-isolated ERG a-wave amplitude was analyzed to determine Tc, the time to initiation of rod recovery, and T50, the time from initiation to 50% of full recovery. Phototransduction was assessed from the fit of a quantitative model to the leading edges of rod-isolated ERG a-waves. ERG a- and b-wave amplitudes and implicit times were also measured. RESULTS: Rod recovery (T50) was delayed by 30% and ERG implicit times by 5% in monkeys in the low ALA group compared with the other groups. There was no significant effect of diet on ERG amplitudes, the time to initiation of rod recovery, or the parameters describing phototransduction. CONCLUSIONS: The results indicate that mechanisms involved in deactivation and rod recovery are selectively altered in monkeys raised on a low-ALA diet whereas, at the flash intensities used, the mechanisms underlying phototransduction remain unaffected.
Assuntos
Células Fotorreceptoras Retinianas Bastonetes/fisiologia , Visão Ocular/fisiologia , Ácido alfa-Linolênico/deficiência , Animais , Gorduras Insaturadas na Dieta/administração & dosagem , Ácidos Docosa-Hexaenoicos/metabolismo , Eletrorretinografia , Macaca mulattaRESUMO
PURPOSE: To compare retinal light damage in rats with either normal or reduced levels of rod outer segment (ROS) docosahexaenoic acid. METHODS: Weanling male albino rats were maintained in a weak cyclic light environment and fed either a nonpurified control diet or a purified diet deficient in the linolenic acid precursor of docosahexaenoic acid (DHA). Half the rats on the deficient diet were given linseed oil, containing more than 50 mol% linolenic acid, once a week to maintain ROS DHA at near normal levels. Diets and linseed oil supplementation were continued for 7 to 12 weeks. To replenish DHA in their ROS, some 10-week-old rats on the deficient diet were given linseed oil three times a week for up to 3 additional weeks. Groups of animals were killed at various times for ROS fatty acid determinations or were exposed to intense green light using intermittent or hyperthermic light treatments. The extent of retinal light damage was determined biochemically by rhodopsin or photoreceptor cell DNA measurements 2 weeks after exposure and morphologically by light and electron microscopy at various times after light treatment. RESULTS: Rats maintained for 7 to 12 weeks on the linolenic acid-deficient diet had significantly lower levels of DHA and significantly higher levels of n-6 docosapentaenoic acid (22:5n-6) in their ROS than deficient-diet animals supplemented once a week with linseed oil or those fed the nonpurified control diet. As determined by rhodopsin levels and photoreceptor cell DNA measurements, deficient diet rats exhibited protection against retinal damage from either intermittent or hyperthermic light exposure. However, the unsaturated fatty acid content of ROS from all three dietary groups was the same and greater than 60 mol%. In 10 week-old deficient-diet rats given linseed oil three times a week, ROS DHA was unchanged for the first 10 days, whereas 22:5n-6 levels declined by 50%. After 3 weeks of treatment with linseed oil, ROS DHA and 22:5n-6 were nearly the same as in rats supplemented with linseed oil from weaning. The time course of susceptibility to retinal light damage, however, was different. Hyperthermic light damage in rats given linseed oil for only 2 days was the same as for rats always fed the deficient diet. Six days after the start of linseed oil treatment, retinal light damage was the same as in rats given the linseed oil supplement from weaning. Morphologic alterations in ROS of linseed oil-supplemented rats immediately after intermittent light exposure were more extensive than in either the deficient-diet animals or those fed the control diet. The deficient-diet rats also exhibited better preservation of photoreceptor cell nuclei and structure 2 weeks after exposure. CONCLUSIONS: Rats fed a diet deficient in the linolenic acid precursor of DHA are protected against experimental retinal light damage. The relationship between retinal light damage and ROS lipids does not depend on the total unsaturated fatty acid content of ROS; the damage appears to be related to the relative levels of DHA and 22:5n-6.
Assuntos
Ácidos Docosa-Hexaenoicos/metabolismo , Luz/efeitos adversos , Lesões Experimentais por Radiação/prevenção & controle , Retina/efeitos da radiação , Segmento Externo da Célula Bastonete/metabolismo , Animais , DNA/análise , Gorduras na Dieta/administração & dosagem , Gorduras Insaturadas na Dieta/administração & dosagem , Ácidos Graxos/metabolismo , Masculino , Células Fotorreceptoras/patologia , Células Fotorreceptoras/efeitos da radiação , Lesões Experimentais por Radiação/metabolismo , Lesões Experimentais por Radiação/patologia , Ratos , Ratos Sprague-Dawley , Retina/metabolismo , Retina/patologia , Rodopsina/metabolismo , Segmento Externo da Célula Bastonete/efeitos da radiação , Ácido alfa-Linolênico/deficiênciaRESUMO
Female OF1 mice were fed on a diet deficient in alpha-linolenic acid or on a control diet 3 weeks before mating and throughout pregnancy and lactation. Pups fed on the same diet as their mothers were used for experiments. The effects of dietary alpha-linolenic acid deficiency were studied in a model of learning, the Morris water maze, and on the following effects of morphine: increase in locomotor activity, modifications of rectal temperature and analgesia. In the place and in the cue versions of the Morris water maze, learning occurred at the same speed in the two diet groups; however, in the place version of the test, the level of the performance was significantly lower in the deficient mice. The probe trial and the extinction procedure did not show any difference between the two diet groups. The morphine-induced increase in locomotor activity occurred significantly earlier and was greater in the deficient diet group. Morphine induced an early hypothermia followed by a late hyperthermia; the hypothermia was significantly greater and the hyperthermia significantly smaller in the deficient mice. The pain thresholds and the morphine-induced analgesia were unmodified by the dietary deficiency. The plasma levels of morphine were similar in the two diet groups.
Assuntos
Aprendizagem em Labirinto/efeitos dos fármacos , Morfina/farmacologia , Entorpecentes/farmacologia , Ácido alfa-Linolênico/deficiência , Analgésicos Opioides/farmacologia , Animais , Temperatura Corporal/efeitos dos fármacos , Sinais (Psicologia) , Dieta , Extinção Psicológica/efeitos dos fármacos , Ácidos Graxos/metabolismo , Feminino , Camundongos , Camundongos Endogâmicos , Morfina/farmacocinética , Atividade Motora/efeitos dos fármacos , Entorpecentes/farmacocinética , Medição da Dor/efeitos dos fármacos , Prosencéfalo/metabolismoRESUMO
The effects of alpha-linolenic acid diet deficiency on rat dopaminergic metabolism were investigated in the frontal cortex of male 2-3 month-old rats using the microdialysis method. Increased basal levels of dopamine metabolites were observed in the frontal cortex of awake deficient rats, without modification of dopamine levels. Moreover, using KCl perfusion which releases newly synthesized dopamine, no difference was observed in anaesthetized deficient rats versus control rats. In addition, a decrease in dopamine release was observed in anaesthetized deficient rats versus control rats after tyramine stimulation, which is known to induce release of dopamine from vesicular stores. A working model is proposed which suggests that a chronic n-3 polyunsaturated fatty acids (PUFA) deficiency may lead to modifications in the internalization of dopamine in the storage pool in the frontal cortex.
Assuntos
Dieta com Restrição de Gorduras/efeitos adversos , Gorduras Insaturadas na Dieta/administração & dosagem , Dopamina/metabolismo , Lobo Frontal/metabolismo , Ácido alfa-Linolênico/deficiência , Análise de Variância , Animais , Feminino , Lobo Frontal/efeitos dos fármacos , Masculino , Microdiálise/métodos , Perfusão , Ratos , Ratos Wistar , Técnicas Estereotáxicas , Transmissão Sináptica/efeitos dos fármacos , Tiramina/administração & dosagem , Ácido alfa-Linolênico/administração & dosagemRESUMO
Three weeks before mating, two groups of SWISS OF1 mice were fed a diet that was similar but contained either peanut oil poor in alpha-linolenic acid [18:3(n-3)] (n-3 deficient = deficient mice = (n-3)-) or peanut + rapeseed oil rich in alpha-linolenic acid (n-3 nondeficient = controls = (n-3)+). Pups, fed the same diet as their dams, aged 45 to 62 days were used for brain lipid analysis and for behavioral experiments, aimed at determining whether there is a relation between the dietary intake of alpha-linolenate and a simple form of learning: habituation. The behavior of mice was compared using four models: exploration recorded in a photocell actimeter, activity in an open-field, duration of immobility in the forced swimming test and number of escape attempts from a small closed space. Habituation was measured by testing the mice in the same situation after some time had elapsed since the first test. Exploration in the photocell actimeter was significantly reduced between day 1 and 4 in nondeficient mice, but, not in deficient mice. The number of square crossings in the open-field was significantly reduced on the second test neither in the control nor in the deficient mice. In the forced swimming test, the habituation (increase in duration of immobility) was significantly greater (255%) in nondeficient than in deficient mice (163%). In the escape attempt experiment, the habituation showed a trend to be greater in controls than in deficient mice (p = 0.061) and was significantly greater in females than in males (p = 0.028). These results suggest that a simple form of learning, habituation, occurs more slowly in mice fed a diet deficient in alpha-linolenic acid.
Assuntos
Comportamento Animal , Gorduras na Dieta/administração & dosagem , Ácido alfa-Linolênico/deficiência , Animais , Feminino , Masculino , Camundongos , GravidezRESUMO
Mice were fed a diet deficient in alpha-linolenic acid [18:3 (n-3)] or a control diet and the effect of this deficiency was assessed by behavioral and pharmacological measurements. Three weeks before mating female mice were fed a diet containing either peanut oil poor in alpha-linolenic acid (n-3)- or peanut+rapeseed oil rich in alpha-linolenic acid (n-3)+ = controls. Pups, aged 47 to 61 days, fed the same diet as their dams, were used for behavioral experiments. Muscular function and neuromuscular coordination assessed by the traction test, the elevated rotarod test and swimming endurance were unchanged by the (n-3)- deficiency. The level of anxiety assessed by the elevated plus-maze (anxiety protocol), the light-dark transition and the neophobia tests did not differ between (n-3)- and control (n-3)+ mice. Defensive behavior was not changed by the diet. The pentobarbital-induced loss of the righting reflex had the same duration in males, females, and controls as in (n-3) deficient mice; the latency to pentobarbital-induced loss of the righting reflex was significantly shorter in females than in males but did not differ according to the diet. Mice fed the (n-3)- deficient diet showed less efficient learning in the elevated plus-maze (learning protocol) and poorer understanding of the situation (or less motivation to escape) in the low rotarod test than mice fed the control (n-3)+ diet.
Assuntos
Ansiedade/fisiopatologia , Comportamento Animal/fisiologia , Cognição/fisiologia , Junção Neuromuscular/fisiologia , Ácido alfa-Linolênico/deficiência , Animais , Dieta , Feminino , Masculino , Camundongos , Atividade Motora/fisiologia , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Junção Neuromuscular/metabolismo , Pentobarbital/farmacologia , Fosfolipídeos/metabolismoRESUMO
We have previously reported that the relative content of 18:3 omega 3 in adipose triglyceride (TG) of women was reduced following major weight loss while on a very low calorie diet (VLCD). In an attempt to prevent this loss of 18:3 omega 3 reserves, we have tested two VLCD supplemented with varying amounts of 18:3 omega 3. The formula (FORM) and food VLCD (2.1-3.0 MJ or 500-700 kcal/d) contained 20 g/d of fat and provided the recommended dietary allowance for minerals and vitamins. FORM subjects (Group 1) were 5 women [initial body mass index (BMI) of 36.8, 168% ideal body weight (IBW) who received 20 g/d of canola oil (1.6 g 18:3 omega 3). Their mean weight loss was 23.9 kg in a 4-5 mon period. Food VLCD subjects (Group 2) were 6 women (BMI 33.9, 155% IBW) supplemented with 2 g/d of linseed oil (1.1 g 18:3 omega 3). Their mean weight loss was 17.4 kg in a 2-3 mon period. Needle biopsies of adipose tissue were obtained from Group 1 before, at midpoint and after weight loss; and from Group 2 before and after weight loss. The adipose TG and serum (Group 1) were separated and their fatty acid composition determined by thin-layer and gas chromatography. In Group 1, adipose 18:3 omega 3 fell from 0.65 to 0.59 wt%, then to 0.52 wt% during weight loss. In Group 2, it fell from 0.77 to 0.64 wt%. The fall in adipose 18:3 omega 3 with weight loss was significant at P = 0.01 (Group 1) and P < 0.01 (Group 2).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Tecido Adiposo/metabolismo , Dieta Redutora , Obesidade/metabolismo , Redução de Peso/fisiologia , Ácido alfa-Linolênico/metabolismo , Adulto , Composição Corporal , Ácidos Graxos/sangue , Feminino , Humanos , Fosfolipídeos/sangue , Triglicerídeos/sangue , Triglicerídeos/química , Ácido alfa-Linolênico/administração & dosagem , Ácido alfa-Linolênico/sangue , Ácido alfa-Linolênico/deficiênciaRESUMO
The changes in guinea pig brain (cerebrum) glycerophospholipid molecular species resulting from a low-alpha linolenic acid (ALA) diet are described. Two groups of six guinea pigs were raised from birth to 16 wk of age on either an n-3 deficient diet containing 0.01 g ALA/100 g diet or n-3 sufficient diet containing 0.71 g ALA/100 g diet. Molecular species of diradyl glycerophosphoethanolamine (GroPEtn), glycerophosphocholine, glycerophosphoserine, and glycerophosphoinositol were analyzed by high-performance liquid chromatography with on-line electrospray ionization mass spectrometry (HPLC/ESI/MS). Alkenylacyl GroPEtn species were determined by comparing spectra before and after mild acid treatment while diacyl- and alkylacyl species were distinguished by HPLC/ESI/MS. The proportions of phospholipid classes and of the diradyl GroPEtn subclasses were not altered by diet changes. The main polyunsaturated molecular species of diradyl GroPEtn subclasses and of phosphatidyl choline and phosphatidylserine (PtdSer) contained 16:0, 18:0, or 18:1 in combination with docosahexaenoic acid (DHA, 22:6n-3), docosapentaenoic (DPA, 22:5n-6), or arachidonic acid (ARA, 20:4n-6). A significant proportion of DPA containing species were present in both diet groups, but in n-3 fatty acid deficiency, the proportion of DPA increased and DHA was primarily replaced by DPA. The combined value of main DHA and DPA containing species in the n3 deficient group ranged from 91-111% when compared with the n-3 sufficient group, indicating a nearly quantitative replacement. The n-3 fatty acid deficiency did not lower the content of ARA containing molecular species of PtdSer of the guinea pig brain as reported previously for the rat brain. The molecular species of phosphatidylinositol were not altered by n-3 fatty acid deficiency. The present data show that the main consequence of a low ALA diet is the preferential replacement of DHA-containing molecular species by DPA-containing molecular species in alkenylacyl- and diacyl GroPEtn and PtdSer of guinea pig brain.
Assuntos
Encéfalo/metabolismo , Dieta , Glicerofosfolipídeos/metabolismo , Ácido alfa-Linolênico/deficiência , Animais , Encéfalo/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Ácidos Graxos/análise , Feminino , Cobaias , Espectrometria de Massas , Fosfolipídeos/análise , Fosfolipídeos/química , Ácido alfa-Linolênico/administração & dosagem , Ácido alfa-Linolênico/metabolismo , Ácido alfa-Linolênico/farmacologiaRESUMO
During heat treatment, polyunsaturated fatty acids and specifically 18:3n-3 can undergo geometrical isomerization. In rat tissues, 18:3 delta 9c,12c,15t, one of the trans isomers of linolenic acid, can be desaturated and elongated to give trans isomers of eicosapentaenoic and docosahexaenoic acids. The present study was undertaken to determine whether such compounds are incorporated into brain structures that are rich in n-3 long-chain polyunsaturated fatty acids. Two fractions enriched in trans isomers of alpha-linolenic acid were prepared and fed to female adult rats during gestation and lactation. The pups were killed at weaning. Synaptosomes, brain microvessels and retina were shown to contain the highest levels (about 0.5% of total fatty acids) of the trans isomer of docosahexaenoic acid (22:6 delta 4c,7c,10c,13c,16c,19t). This compound was also observed in myelin and sciatic nerve, but to a lesser extent (0.1% of total fatty acids). However, the ratios of 22:6 trans to 22:6 cis were similar in all the tissues studied. When the diet was deficient in alpha-linolenic acid, the incorporation of trans isomers was apparently doubled. However, comparison of the ratios of trans 18:3n-3 to cis 18:3n-3 in the diet revealed that the cis n-3 fatty acids were more easily desaturated and elongated to 22:6n-3 than the corresponding trans n-3 fatty acids. An increase in 22:5n-6 was thus observed, as has previously been described in n-3 fatty acid deficiency. These results encourage further studies to determine whether or not incorporations of such trans isomers into tissues may have physiological implications.
Assuntos
Encéfalo/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Troca Materno-Fetal , Retina/metabolismo , Animais , Encéfalo/irrigação sanguínea , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Feminino , Temperatura Alta , Isomerismo , Lactação , Bainha de Mielina/metabolismo , Gravidez , Ratos , Ratos Wistar , Nervo Isquiático/metabolismo , Sinaptossomos/metabolismo , Ácido alfa-Linolênico/deficiência , Ácido alfa-Linolênico/metabolismoRESUMO
The authors previously reported that the milk of Yoruba women in southwestern Nigeria was deficient in alpha-linolenic acid and contained a high percentage (42%) of medium chain-length fatty acids (MCFA, C10-C14). In the present study, the authors used capillary gas-liquid chromatography to analyze the milk of Hausa women in the northern region of Nigeria. The milk of the Hausa women contained 27% MCFA, 10.6% linoleic acid, 0.41% alpha-linolenic acid, 0.52% arachidonic acid, and 0.32% docosahexaenoic acid. The proportion of alpha-linolenic acid in the serum phospholipids of a subset of exclusively breastfed infants (n = 15; mean age, 6.2 +/- 0.3 months) was below the limit of detection (< 0.03%). While the milk of women in northern Nigeria is adequate with regard to n-3 and n-6 fatty acids, to satisfy the requirements for alpha-linolenic acid, it may be necessary to supplement the infants of these women after the first 6 months of life.
Assuntos
Ácidos Graxos/análise , Leite Humano/química , Adulto , Aleitamento Materno , Cromatografia Gasosa , Ácidos Graxos/sangue , Feminino , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Nigéria , Avaliação Nutricional , Fatores de Tempo , Ácido alfa-Linolênico/análise , Ácido alfa-Linolênico/sangue , Ácido alfa-Linolênico/deficiênciaRESUMO
Lipids are important cell components, both from the structural and the functional point of view. Besides, they intervene in transporting functions, cell recognition and immunity. Essential Fatty Acids (EFA) are important for the functional and structural maintenance of animal organisms. In our laboratory, it was demonstrated that one group of pregnant rats fed on an EFA deficient diet, and other group of rats fed on the same diet but with 5% of corn oil (rich in linoleic acid) showed alterations on the development of the metrial gland. In the present work, 57 female rats of a Wistar strain were fed since weaning with one of the following diets: EFAD: deficient in essential fatty acids, COD: EFAD + 5% corn oil (linoleic acid sufficient but alpha-linoleic acid deficient); SAD: EFAD + 5% soy oil (both EFA sufficient) and CD: commercial diet. After 3 months the animals were sacrificed on the 13 th. day of gestation. Uteru's horns were dissected and the implantation sities were fixed on formol and embebbed in parafin. The observations were carried out with H/E coloured cross-sections and the corialantoidea placenta, the cities of implantations and the sitios of reabsortions were studied. The metrial gland of DAGE and DAM rats presented structural modifications compared to DC rats. The most relevant findings were: indifferentiation of the granulated metrial gland cells and an increase in the amount of connective tissue. In DAS rats, on the contrary, the aspect of the metrial gland was similar to the observed in the DC group. In the DAGE and the DAM groups Labyrinthium was enlarged with vascular septum group. Mean while DAS was similar to group DC (thin and vascular). Differences in the cities of implantations and reabsortions were not detected. The present results suggest that alpha-linolenico acid is essential for the rat placenta to reach normal development.